Autoantibodies to Ganglionic Acetylcholine Receptors in Autoimmune Autonomic Neuropathies

Abstract

Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmune autonomic neuropathy and distinguishes these disorders from other types of dysautonomia. The positive correlation between high levels of ganglionic-receptor antibodies and the severity of autonomic dysfunction suggests that the antibodies have a pathogenic role in these types of neuropathy.

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

“…(Vernino et al 2000). Low, but positive titres of antibodies to P/Q VGCCs were also found in 4 out of 10 patients with CIPO (Knowles et al 2002).…”

“…Most common in this context are type 1 anti-neuronal nuclear autoantibodies (ANNA-1, also known as anti-Hu), which recognise neuron-specific RNA binding proteins expressed by central and peripheral neurons, including enteric neurons, and SCLC tumour cells (Bell et al 1976;Lucchinetti et al 1998;Lee et al 2001). Antibodies targeting cell-surface channels have been detected in smaller numbers of cases, including anti-N-type VGCCs with SCLC, retroperitoneal Bcell lymphoma, ovarian and breast carcinoma Dhamija et al 2008), anti-P/Q-type VGCCs with SCLC (Pardi et al 2002), anti-VGKCs with thymoma (Viallard et al 2005) and anti-ganglionic α3 nAChR antibodies with SCLC, thymoma, bladder and rectal carcinoma (Vernino et al 2000).…”

“…AGID represents a group of patients who have a limited form of dysautonomia with prominent GI symptoms of hyper-or hypo-motility and one or more autoantibodies against cellsurface cation channels and includes GI dysmotility secondary to neoplasia, diabetes mellitus and hypothyroidism. It may also occur idiopathically as a manifestation of autoimmune autonomic neuropathies Vernino et al 2000). Although the study by Dhamija et al screened 29 cases, only 8 of these could be considered as primary GINMD, the others having neoplasia and / or other disease.…”

Autoimmune diseases involving nicotinic receptors

“…Nicotinic acetylcholine receptors (AChRs) are the targets of both autoimmune and genetic diseases (Drachman, 1994;Lindstrom, 2000aLindstrom, , 2002aVernino et al, 2000;Grando, 2000;Engel et al, 1999Engel et al, , 2002aSteinlein, 2000;Kuryatov et al, 1997;De Fusco et al, 2000;Phillips et al, 2001). For both types of pathologies, initially myasthenias rather than neuronal AChR diseases were discovered because we better understand the functional role of muscle AChRs and most easily recognized the effects on neuromuscular transmission of pathologies resulting from decreasing or increasing AChR function.…”

“…Neuronal AChRs have more recently been discovered to be the objects of both autoimmune and genetic diseases (Vernino et al, 2000;Grando, 2000;Steinlein, 2000;Kuryatov et al, 1997;DeFusco et al, 2000;Phillips et al, 2001). The major barrier to recognizing the pathological bases of diseases resulting from altered neuronal AChR function is that we know so little about the normal functional roles of the many subtypes of neuronal AChRs (Lindstrom, 2000b).…”